The nematode C. elegans has been a discovery engine for regulation of animal lifespan. We propose to follow up our surprising discovery that decreases in insulin-like signaling induce a dramatic increase in lifespan in C. elegans that is intimately associated with expression of germline-specific pathways in the somatic cells. We will dissect how these genes are regulated by insulin-like signaling and how the somatic expression of germline genes contributes to the increase in longevity. Because essentially all of the genes proposed to be studied in this proposal are conserved in humans, and because the insulin pathway has already been shown to act in human longevity, the pathways we dissect are likely to be applicable to human longevity. PUBLIC HEALTH RELEVANCE: The nematode C. elegans has been a discovery engine for regulation of animal lifespan. Because essentially all of the genes proposed to be studied in this proposal are conserved in humans, and because the insulin pathway has already been shown to act in human longevity, the pathways we dissect are likely to be applicable to human longevity.